Diclofenac sodium is a non-steroidal pharmaceutical having excellent anti-inflammatory analgesic effects and, along with indomethacin having similar drug efficacy, is one of pharmaceuticals which are most widely used. This diclofenac sodium is now furnished or sold on the market only in the unit dosage form of oral preparations and suppositories. When orally administered, non-steroidal anti-inflammatory analgesics such as diclofenac sodium and indomethacin are however known to develop side effects such as gastrointestinal problems depending on the dose. In particular, even if an inflamed part to which administration is intended is a local part such as a joint or a part around the joint, the administration of an oral preparation or a suppository also requires to increase the drug concentrations in parts other than the inflamed part in order to obtain an effective drug concentration in the affected part. This has led to the administration of non-steroidal anti-inflammatory analgesics at excessively high doses, thereby arousing concerns about such side effects as mentioned above.
Research and development work has therefore been conducted on topical dosage forms of non-steroidal anti-inflammatory analgesics. For substances having relatively high lipophilicity such as indomethacin and ketoprofen, topical transdermal preparations such as external liquid preparations, ointments and plasters have already been furnished and are available on the market. Concerning diclofenac sodium, however, it is the current situation that no practically acceptable transdermal preparation is available yet due to difficulty in stably dissolving it in a base.
Described specifically, diclofenac sodium itself has solubility of about 1.5 wt. % (hereinafter referred to simply as "%") in water but, when various base ingredients are added to formulate it into an external medicinal preparation, becomes very prone to crystallization. It is therefore the current situation that no solution of diclofenac sodium is actually available in a form suited for use in the formulation of a medicinal preparation.
As a method for dissolving diclofenac sodium in a solution, there is now known a technique in which diclofenac sodium is dissolved using a lower alcohol such as ethanol or isopropanol and the resulting solution is then formulated into a medicinal preparation. However, a lower alcohol has high volatility and hence involves drawbacks in that it imposes a limitation on the available unit dosage form and tends to cause irritation on skin. Such a lower alcohol is thus not considered to be suitable for the manufacture of medicinal products.
It has therefore been desired to develop a technique that makes it possible to keep diclofenac sodium stably dissolved in water without relying upon such a lower alcohol and even after addition of base ingredient for formulation into a unit dosage form.